Trial Outcomes & Findings for Topical Sirolimus for the Treatment of Pachyonychia Congenita (PC) (NCT NCT02152007)
NCT ID: NCT02152007
Last Updated: 2016-10-07
Results Overview
The primary outcome measure for this Phase 1b safety study is evaluation of system absorption through measurement of serum sirolimus trough levels. The limit of detection of the assay was 2.0 ng/mL.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
15 participants
Primary outcome timeframe
Two weeks and every 1-2 months for 24 weeks or within 2 weeks after the last dose of study drug
Results posted on
2016-10-07
Participant Flow
Participant milestones
| Measure |
Split-body 1% Sirolimus Cream (TD201 1%)
This is a split-body design. Subjects will self-administer 1% topical sirolimus cream or placebo cream (no drug, vehicle control) on the plantar surface of each foot. At least one foot will be treated with topical sirolimus at some time during the study. Application will be one time daily for a total of 26 weeks. There will be an additional follow-up visit 3 months after the last application of study drug. The total duration of the study is 39 weeks.
1% sirolimus cream (TD201 1%): 1% sirolimus cream (TD201 1%)
|
|---|---|
|
Overall Study
STARTED
|
15
|
|
Overall Study
COMPLETED
|
14
|
|
Overall Study
NOT COMPLETED
|
1
|
Reasons for withdrawal
| Measure |
Split-body 1% Sirolimus Cream (TD201 1%)
This is a split-body design. Subjects will self-administer 1% topical sirolimus cream or placebo cream (no drug, vehicle control) on the plantar surface of each foot. At least one foot will be treated with topical sirolimus at some time during the study. Application will be one time daily for a total of 26 weeks. There will be an additional follow-up visit 3 months after the last application of study drug. The total duration of the study is 39 weeks.
1% sirolimus cream (TD201 1%): 1% sirolimus cream (TD201 1%)
|
|---|---|
|
Overall Study
Withdrawal by Subject
|
1
|
Baseline Characteristics
Topical Sirolimus for the Treatment of Pachyonychia Congenita (PC)
Baseline characteristics by cohort
| Measure |
Split-body 1% Sirolimus Cream (TD201 1%)
n=15 Participants
This is a split-body design. Subjects will self-administer 1% topical sirolimus cream or placebo cream (no drug, vehicle control) on the plantar surface of each foot. At least one foot will be treated with topical sirolimus at some time during the study. Application will be one time daily for a total of 26 weeks. There will be an additional follow-up visit 3 months after the last application of study drug. The total duration of the study is 39 weeks.
1% sirolimus cream (TD201 1%): 1% sirolimus cream (TD201 1%)
|
|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
15 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
9 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
6 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
2 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
13 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
15 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Two weeks and every 1-2 months for 24 weeks or within 2 weeks after the last dose of study drugPopulation: Starting at week 13, visit 4, there were only 14 participants with available data.
The primary outcome measure for this Phase 1b safety study is evaluation of system absorption through measurement of serum sirolimus trough levels. The limit of detection of the assay was 2.0 ng/mL.
Outcome measures
| Measure |
Split-body 1% Sirolimus Cream (TD201 1%)
n=15 Participants
This is a split-body design. Subjects will self-administer 1% topical sirolimus cream or placebo cream (no drug, vehicle control) on the plantar surface of each foot. At least one foot will be treated with topical sirolimus at some time during the study. Application will be one time daily for a total of 26 weeks. There will be an additional follow-up visit 3 months after the last application of study drug. The total duration of the study is 39 weeks.
1% sirolimus cream (TD201 1%): 1% sirolimus cream (TD201 1%)
|
Placebo Cream (Vehicle Control)
Placebo Cream (Vehicle Control)
|
|---|---|---|
|
Evaluation of Systemic Absorption Through Measurement of Serum Sirolimus Trough Levels
Visit 1, Baseline, <2.0 ng/mL
|
15 participants
|
—
|
|
Evaluation of Systemic Absorption Through Measurement of Serum Sirolimus Trough Levels
Visit 2, Week 3, <2 ng/mL
|
15 participants
|
—
|
|
Evaluation of Systemic Absorption Through Measurement of Serum Sirolimus Trough Levels
Visit 3, Week 7, <2 ng/mL
|
15 participants
|
—
|
|
Evaluation of Systemic Absorption Through Measurement of Serum Sirolimus Trough Levels
Visit 4, Week 13, <2 ng/mL
|
14 participants
|
—
|
|
Evaluation of Systemic Absorption Through Measurement of Serum Sirolimus Trough Levels
Visit 5, Week 17, <2 ng/mL
|
14 participants
|
—
|
|
Evaluation of Systemic Absorption Through Measurement of Serum Sirolimus Trough Levels
Visit 6, Week 25, <2 ng/mL
|
14 participants
|
—
|
|
Evaluation of Systemic Absorption Through Measurement of Serum Sirolimus Trough Levels
Visit 7, Week 37, <2 ng/mL
|
14 participants
|
—
|
SECONDARY outcome
Timeframe: Weekly for 39 weeksPatient-reported weekly assessment in the PC Quality of Life Index
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Weekly for 39 weeksOutcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: Prior to application of study drug and within 15-45 minutes after application of study drug at each visit for 39 weeksInvestigator assessment of local tolerability at the application sites on the plantar surfaces will be evaluated by the Investigator according to a 4-point scale (0, 1, 2, or 3; none to severe) with regard to: erythema, pruritis, stinging/burning, and crusting/erosion
Outcome measures
| Measure |
Split-body 1% Sirolimus Cream (TD201 1%)
n=15 Participants
This is a split-body design. Subjects will self-administer 1% topical sirolimus cream or placebo cream (no drug, vehicle control) on the plantar surface of each foot. At least one foot will be treated with topical sirolimus at some time during the study. Application will be one time daily for a total of 26 weeks. There will be an additional follow-up visit 3 months after the last application of study drug. The total duration of the study is 39 weeks.
1% sirolimus cream (TD201 1%): 1% sirolimus cream (TD201 1%)
|
Placebo Cream (Vehicle Control)
n=15 Participants
Placebo Cream (Vehicle Control)
|
|---|---|---|
|
Investigator Assessment of Local Tolerability
Visit 1 Pre, Erythema Score (0-3)
|
0.2 units on a scale
Standard Deviation 0.41
|
0.2 units on a scale
Standard Deviation 0.41
|
|
Investigator Assessment of Local Tolerability
Visit 1 Pre, Pruritus Score (0-3)
|
0.1 units on a scale
Standard Deviation 0.26
|
0 units on a scale
Standard Deviation 0
|
|
Investigator Assessment of Local Tolerability
Visit 1 Pre, Stinging/Burning (0-3) Score
|
0 units on a scale
Standard Deviation 0
|
0.1 units on a scale
Standard Deviation 0.26
|
|
Investigator Assessment of Local Tolerability
Visit 1 Pre, Crusting/Erosion Score (0-3)
|
0.1 units on a scale
Standard Deviation 0.26
|
0.1 units on a scale
Standard Deviation 0.26
|
|
Investigator Assessment of Local Tolerability
Visit 1 Post, Erythema Score (0-3)
|
0.2 units on a scale
Standard Deviation 0.41
|
0.2 units on a scale
Standard Deviation 0.41
|
|
Investigator Assessment of Local Tolerability
Visit 1 Post, Pruritus Score (0-3)
|
0 units on a scale
Standard Deviation 0
|
0 units on a scale
Standard Deviation 0
|
|
Investigator Assessment of Local Tolerability
Visit 1 Post, Stinging/Burning Score (0-3)
|
0 units on a scale
Standard Deviation 0
|
0.1 units on a scale
Standard Deviation 0.26
|
|
Investigator Assessment of Local Tolerability
Visit 1 Post, Crusting/Erosion Score (0-3)
|
0.1 units on a scale
Standard Deviation 0.26
|
0.1 units on a scale
Standard Deviation 0.26
|
|
Investigator Assessment of Local Tolerability
Visit 4 Pre, Erythema Score (0-3)
|
0 units on a scale
Standard Deviation 0
|
0 units on a scale
Standard Deviation 0
|
|
Investigator Assessment of Local Tolerability
Visit 4 Pre, Pruritus Score (0-3)
|
0.1 units on a scale
Standard Deviation 0.28
|
0.1 units on a scale
Standard Deviation 0.28
|
|
Investigator Assessment of Local Tolerability
Visit 4 Pre, Stinging/Burning Score (0-3)
|
0.1 units on a scale
Standard Deviation 0.28
|
0 units on a scale
Standard Deviation 0
|
|
Investigator Assessment of Local Tolerability
Visit 4 Pre, Crusting/Erosion Score (0-3)
|
0.1 units on a scale
Standard Deviation 0.28
|
0.2 units on a scale
Standard Deviation 0.38
|
|
Investigator Assessment of Local Tolerability
Visit 4 Post, Erythema Score (0-3)
|
0 units on a scale
Standard Deviation 0
|
0 units on a scale
Standard Deviation 0
|
|
Investigator Assessment of Local Tolerability
Visit 4 Post, Pruritus Score (0-3)
|
0 units on a scale
Standard Deviation 0
|
0 units on a scale
Standard Deviation 0
|
|
Investigator Assessment of Local Tolerability
Visit 4 Post, Stinging/Burning Score (0-3)
|
0.1 units on a scale
Standard Deviation 0.28
|
0 units on a scale
Standard Deviation 0
|
|
Investigator Assessment of Local Tolerability
Visit 4 Post, Crusting/Erosion Score (0-3)
|
0.1 units on a scale
Standard Deviation 0.28
|
0.2 units on a scale
Standard Deviation 0.38
|
|
Investigator Assessment of Local Tolerability
Visit 7 Pre, Erythema Score (0-3)
|
0.2 units on a scale
Standard Deviation 0.58
|
0.2 units on a scale
Standard Deviation 0.58
|
|
Investigator Assessment of Local Tolerability
Visit 7 Pre, Pruritus Score (0-3)
|
0.2 units on a scale
Standard Deviation 0.58
|
0.2 units on a scale
Standard Deviation 0.58
|
|
Investigator Assessment of Local Tolerability
Visit 7 Pre, Stinging/Burning Score (0-3)
|
0.3 units on a scale
Standard Deviation 0.61
|
0.3 units on a scale
Standard Deviation 0.61
|
|
Investigator Assessment of Local Tolerability
Visit 7 Pre, Crusting/Erosion Score (0-3)
|
0.4 units on a scale
Standard Deviation 0.65
|
0.3 units on a scale
Standard Deviation 0.61
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Each study visit over 39 weeksAn expert in the disease who is blinded to the study treatment will read the photographs of the callus area taken at each study visit. The reader will assess changes to the calluses based on criteria such as blisters, cracks, small/large size, and red or bloody spots on the callus. Change in calluses will be reported for both the right and left foot.
Outcome measures
Outcome data not reported
Adverse Events
Split-body 1% Sirolimus Cream (TD201 1%)
Serious events: 0 serious events
Other events: 6 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Split-body 1% Sirolimus Cream (TD201 1%)
n=15 participants at risk
This is a split-body design. Subjects will self-administer 1% topical sirolimus cream or placebo cream (no drug, vehicle control) on the plantar surface of each foot. At least one foot will be treated with topical sirolimus at some time during the study. Application will be one time daily for a total of 26 weeks. There will be an additional follow-up visit 3 months after the last application of study drug. The total duration of the study is 39 weeks.
1% sirolimus cream (TD201 1%): 1% sirolimus cream (TD201 1%)
|
|---|---|
|
Gastrointestinal disorders
Nausea
|
6.7%
1/15 • Number of events 1 • Duration of the study, up to 39 weeks
|
|
General disorders
Pyrexia
|
6.7%
1/15 • Number of events 1 • Duration of the study, up to 39 weeks
|
|
Infections and infestations
Upper respiratory tract infection
|
6.7%
1/15 • Number of events 1 • Duration of the study, up to 39 weeks
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
6.7%
1/15 • Number of events 1 • Duration of the study, up to 39 weeks
|
|
Skin and subcutaneous tissue disorders
Dermatitis contact
|
6.7%
1/15 • Number of events 1 • Duration of the study, up to 39 weeks
|
|
Skin and subcutaneous tissue disorders
Skin ulcer
|
6.7%
1/15 • Number of events 1 • Duration of the study, up to 39 weeks
|
|
Skin and subcutaneous tissue disorders
Urticaria
|
6.7%
1/15 • Number of events 1 • Duration of the study, up to 39 weeks
|
|
Nervous system disorders
Headache
|
6.7%
1/15 • Number of events 1 • Duration of the study, up to 39 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Rhinorrhea
|
6.7%
1/15 • Number of events 1 • Duration of the study, up to 39 weeks
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place